3vu7
Crystal structure of REV1-REV7-REV3 ternary complexCrystal structure of REV1-REV7-REV3 ternary complex
Structural highlights
Function[REV1_HUMAN] Deoxycytidyl transferase involved in DNA repair. Transfers a dCMP residue from dCTP to the 3'-end of a DNA primer in a template-dependent reaction. May assist in the first step in the bypass of abasic lesions by the insertion of a nucleotide opposite the lesion. Required for normal induction of mutations by physical and chemical agents.[1] [2] [3] [4] [5] [DPOLZ_HUMAN] Interacts with MAD2L2 to form the error prone DNA polymerase zeta involved in translesion DNA synthesis. [MD2L2_HUMAN] Adapter protein able to interact with different proteins and involved in different biological processes. Mediates the interaction between the error-prone DNA polymerase zeta catalytic subunit REV3L and the inserter polymerase REV1, thereby mediating the second polymerase switching in translesion DNA synthesis. Translesion DNA synthesis releases the replication blockade of replicative polymerases, stalled in presence of DNA lesions. May also regulate another aspect of cellular response to DNA damage through regulation of the JNK-mediated phosphorylation and activation of the transcriptional activator ELK1. Inhibits the FZR1- and probably CDC20-mediated activation of the anaphase promoting complex APC thereby regulating progression through the cell cycle. Regulates TCF7L2-mediated gene transcription and may play a role in epithelial-mesenchymal transdifferentiation.[6] [7] [8] [9] [10] Publication Abstract from PubMedREV1, REV3, and REV7 are pivotal proteins in translesion DNA synthesis, which allows DNA synthesis even in the presence of DNA damage. REV1 and REV3 are error-prone DNA polymerases and function as inserter and extender polymerases in this process, respectively. REV7 interacts with both REV1 and REV3, acting as an adaptor that functionally links the two, although the structural basis of this collaboration remains unclear. Here, we show the crystal structure of the ternary complex, composed of the C-terminal domain of human REV1, REV7, and a REV3 fragment. The REV1 C-terminal domain adopts a four-helix bundle that interacts with REV7. A linker region between helices 2 and 3, which is conserved among mammals, interacts with the beta-sheet of REV7. Remarkably, the REV7-binding interface is distinct from the binding site of DNA polymerase eta or kappa. Thus, the REV1 C-terminal domain might facilitate polymerase switching by providing a scaffold for both inserter and extender polymerases to bind. Our structure reveals the basis of DNA polymerase zeta (a complex of REV3 and REV7) recruitment to the stalled replication fork and provides insight into the mechanism of polymerase switching. Structural basis of recruitment of DNA polymerase zeta by interaction between REV1 and REV7 proteins.,Kikuchi S, Hara K, Shimizu T, Sato M, Hashimoto H J Biol Chem. 2012 Sep 28;287(40):33847-52. Epub 2012 Aug 2. PMID:22859296[11] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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